LONDON – The CEOs of Pfizer Inc. and Astrazeneca plc both say they are on track to make their COVID-19 vaccines available for use before the end of the year and have promised to manufacture at risk, supply at cost and ensure equitable access.
The obvious caveat is that this speedy delivery will only apply if the products are found to be safe and effective.
But Pascal Soriot, CEO of Astrazeneca, Pfizer CEO Albert Bourla, and Paul Stoffels, chief scientific officer of Johnson & Johnson, all highlighted the extent to which the crisis has completely upended the traditional – lengthy – one step at a time approach to vaccines development, when they gave a progress report on their respective products on May 28 during the International Federation of Pharmaceutical Manufacturers and Associations’ virtual press briefing.
The scale of pharma’s response to the pandemic, both in hard cash and opportunity cost was underlined by Bourla, who said Pfizer is investing $2 billion in COVID-19 research. Most of that expenditure will be within the next year for the two mRNA vaccines it is developing with German biotech Biontech SE, and does not include staff costs. “It’s a major undertaking,” Bourla said.
There are multiple technologies in play, from the old-fashioned tried and tested, to novel constructs that have not been used in any approved products, Bourla noted. “The reason we chose mRNA technology, even though it has not been done before, is because we have a two-year collaboration with Biontech on a flu vaccine,” he said. “We felt we had enough expertise, enough scale and could go at speed.”
In view of the need to go as fast as possible, Pfizer started working on the project with Biontech, exchanging materials and information, and investing money, in advance of having a formal contract in place. Bourla said the first phase of clinical development will be completed in June, providing enough data to progress very rapidly through phase II to a phase III trial that will recruit 20,000 – 30,000 participants.
“We are going to move very fast and will manufacture at risk. If it goes well, we will have enough evidence of safety and efficacy so we can feel confident to have a vaccine around the end of October,” said Bourla.
Similarly, Soriot said the decision to work with Oxford University to develop a chimpanzee adenoviral vectored vaccine, is based on the previous experience of the researchers at the university’s Jenner Institute and the speed with which they were able to get the project started.
The 1,000-subject phase I/II trial completed last week, with data due soon, and a phase IIb/III U.K. trial involving 3,000 volunteers is now underway. Astrazeneca also is starting a U.S. trial, after securing up to $1.2 billion from the U.S. COVID-19 vaccines program, Operation Warp Speed.
There is growing concern that with infection rates falling in the northern hemisphere, these trials will take time, or that it will not be possible to complete them. “We are trying to move as quickly as possible because a vaccine is needed, and also because the disease is declining. The focus is on delivering phase III in the U.K. and the U.S. phase III,” said Soriot. Backing those up, trials in Kenya, South Africa and Brazil are due to start soon, he said.
The looming difficulty of getting a fast turn-around in field trials has turned attention to the possibility of doing human challenge trials. Soriot said Astrazeneca has talked to the Oxford University researchers about that, but with no challenge agent or protocol yet in place, it is “much too early” to consider.
“I expect at some time it will be done, but we still have the chance to show efficacy in the normal way,” said Soriot.
Slightly behind Astrazeneca and Pfizer, Johnson & Johnson last week published preclinical data on efficacy and is now doing challenge studies in an animal model to find the right dose for its vaccine, which is based on the platform technology used in the development of the company’s Ebola vaccine, currently in use in the epidemic in the Democratic Republic of Congo.
Stoffels said clinical trials will start later this year, and Johnson & Johnson will deliver 1 billion doses next year. “We are working in parallel on manufacturing and have looked from the beginning at how to upscale,” he said. The company has “worked very hard on stability” to come up with a vaccine that is suitable for use in developing countries that do not have efficient cold chains, in order to ensure equitable access.
Bourla admitted that is an issue for the Pfizer/Biontech vaccine candidates, which need to be stored at minus 8 degrees C. That is not very convenient for Africa, for example, he said. “We are working on second wave products, making sure [they] don’t need temperature control.”
‘Not enough vials in the world’
As the three companies throw huge amounts of expertise, time and cash into development and scale-up, they have all hit the same barrier. It seems banal, but a world shortage of glass vials is standing in the way of delivery.
All three are talking to the regulators to find a workaround. “Typically, [vaccines] are in single-dose vials. We are exploring if it could be five- or 10-dose vials. If acceptable, we can resolve a significant part of the bottleneck of manufacturing,” said Bourla.
Stoffels said that with a cell line that is able to produce 300 million doses in 2,000-liter vessels, scale-up is not the issue. “It’s getting access to fill and finish which is the bottleneck at the moment,” he said.
The same is true for Astrazeneca, with Soriot saying, “The challenge is to fill the vials; there are not enough vials in the world.”
Each of the CEOs expressed concerns about the rising tension over access. “The reality is governments will try to leverage all the influence they have to get access, and we will be caught in the middle,” Bourla said.
For Stoffels, building capacity and volume is “the best answer” to head off the rows about allocation of any approved vaccines. “We have to make the right investments now,” he said.
Soriot said it is not a case of who gets Astrazeneca’s vaccine first. “It will be provided around the world in an equitable manner. That’s why we are setting up separate supply chains [in the U.S., Europe and Asia],” he said.